Interpretive Summary: A significant component of the health care costs in the United States is associated with the care of infants born preterm. A major gut disease in these infants is necrotizing enterocolitis (NEC) and a half million preterm infants are born annually with an increased risk of developing NEC. An important nutritional factor that triggers NEC is formula feeding. Preterm infant formulas contain a mixture of carbohydrates, including lactose and maltodextrins or polycose. The goal of this study was to determine whether the type of carbohydrate present in formula affects the chance of getting NEC. We used preterm piglets as a model to test the question. The study examined the presence of NEC in groups of piglets that were born premature and fed either lactose- or maltodextrin-based formula. The key finding was that the incidence of NEC was much higher in pigs given maltodextrin vs. lactose formula. Additional studies that tested the digestive capacity of the preterm piglets showed that maltodextrin is poorly absorbed, but lactose is well-tolerated. The poor digestion of maltodextrin led to increased production of gut bacteria that seemed to trigger NEC. The findings show that poorly digested carbohydrate, specifically maltodextrin, is sufficient to cause NEC in formula-fed preterm piglets.

Technical Abstract:
Necrotizing enterocolitis (NEC) remains the most severe gastrointestinal disorder in preterm infants. It is associated with the initiation of enteral nutrition and may be related to immature carbohydrate digestive capacity. We tested the hypothesis that a formula containing maltodextrin vs. lactose as the principal source of carbohydrate would predispose preterm pigs to a higher NEC incidence. Cesarean-derived preterm pigs were given total parenteral nutrition (TPN) for 48 hrs followed by 36 hrs of total enteral nutrition with a lactose- (n=11) or maltodextrin-based (n=11) formula. A higher incidence (91 vs. 27%) and severity (scores of 3.3 vs. 1.8) of NEC was observed in the maltodextrin vs. the lactose group. Compared to the lactose group, this higher NEC occurrence in the maltodextrin group was associated with: significantly lower activities of lactase, maltase, and aminopeptidase; reduced villus height; transiently reduced in vivo aldohexose uptake; and reduced ex vivo aldohexose uptake capacity in the mid intestine. The bacterial diversity was low for both diets, but alterations in bacterial composition and luminal concentrations of short chain fatty acids were observed with the maltodextrin diet. In a second study, we quantified net portal absorption of aldohexoses (glucose and galactose) during an acute jejunal infusion of either a maltodextrin- or lactose-based formula (n=8) in preterm pigs. We found lower net portal aldohexose absorption (42 vs. 4%) and increased intestinal recovery of undigested carbohydrate (68 vs. 27%) in pigs acutely perfused with a maltodextrin- compared to a lactose-based formula, respectively. The higher digestion of the lactose relative to the maltodextrin in the formulas can be attributed to a 5- to 20-fold higher hydrolytic activity of tissue-specific lactase compared to maltases. We conclude that carbohydrate maldigestion is sufficient to increase the incidence and severity of NEC in preterm pigs.